Genome-wide scan in a large complex pedigree with predominantly male schizophrenics from the island of Kosrae: evidence for linkage to chromosome 2q.

Details

Serval ID
serval:BIB_5F510E424560
Type
Article: article from journal or magazin.
Collection
Publications
Title
Genome-wide scan in a large complex pedigree with predominantly male schizophrenics from the island of Kosrae: evidence for linkage to chromosome 2q.
Journal
Molecular Psychiatry
Author(s)
Wijsman E.M., Rosenthal E.A., Hall D., Blundell M.L., Sobin C., Heath S.C., Williams R., Brownstein M.J., Gogos J.A., Karayiorgou M.
ISSN
1359-4184 (Print)
ISSN-L
1359-4184
Publication state
Published
Issued date
2003
Peer-reviewed
Oui
Volume
8
Number
7
Pages
695-705, 643
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
It is widely accepted that founder populations hold promise for mapping loci for complex traits. However, the outcome of these mapping efforts will most likely depend on the individual demographic characteristics and historical circumstances surrounding the founding of a given genetic isolate. The 'ideal' features of a founder population are currently unknown. The Micronesian islandic population of Kosrae, one of the four islands comprising the Federated States of Micronesia (FSM), was founded by a small number of settlers and went through a secondary genetic 'bottleneck' in the mid-19th century. The potential for reduced etiological (genetic and environmental) heterogeneity, as well as the opportunity to ascertain extended and statistically powerful pedigrees makes the Kosraen population attractive for mapping schizophrenia susceptibility genes. Our exhaustive case ascertainment from this islandic population identified 32 patients who met DSM-IV criteria for schizophrenia or schizoaffective disorder. Three of these were siblings in one nuclear family, and 27 were from a single large and complex schizophrenia kindred that includes a total of 251 individuals. One of the most startling findings in our ascertained sample was the great difference in male and female disease rates. A genome-wide scan provided initial suggestive evidence for linkage to markers on chromosomes 1, 2, 3, 7, 13, 15, 19, and X. Follow-up multipoint analyses gave additional support for a region on 2q37 that includes a schizophrenia locus previously identified in another small genetic isolate, with a well-established recent genealogical history and a small number of founders, located on the eastern border of Finland. In addition to providing further support for a schizophrenia susceptibility locus at 2q37, our results highlight the analytic challenges associated with extremely large and complex pedigrees, as well as the limitations associated with genetic studies of complex traits in small islandic populations.
Keywords
Adolescent, Adult, Age of Onset, Chromosome Mapping, Chromosomes, Human, Pair 2/genetics, Ethnic Groups/genetics, Female, Finland/ethnology, Founder Effect, Genetic Predisposition to Disease, Genome, Human, Humans, Lod Score, Male, Micronesia/epidemiology, Middle Aged, Parity, Pedigree, Psychotic Disorders/epidemiology, Psychotic Disorders/genetics, Schizophrenia/epidemiology, Schizophrenia/genetics, Sex Distribution
Pubmed
Open Access
Yes
Create date
27/02/2012 16:37
Last modification date
20/08/2019 14:17
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